Adiponectin is a hormone consisting of 244 amino acids, which is secreted from adipose tissue. It was isolated from human adipose tissue in 1996. It is a secretory protein specific for adipose tissue (Non-patent Document 2), and it is present not only in adipose tissue but also in blood in a large amount (5 to 10 μg/ml in healthy people) (Non-patent Document 3). It is known to promote fat burning and uptake of sugar in skeletal muscle and liver by activating AMP kinase (AMP-activated protein kinase: AMPK). It is known that this adiponectin is secreted in a large amount from small adipocytes; however, the secretion volume decreased with the enlargement of adipocytes.
Adiponectin is also known as a beneficial adipocytokine, which suppresses arteriosclerosis. Regarding adipocytokines, in addition to the aforementioned beneficial adipocytokines, there are harmful adipocytokines such as PAI-1 and TNF-α, which promote arteriosclerosis. In a normal state, the secretion volumes of beneficial and harmful adipocytokines are balanced. However, when adipocytes are enlarged due to obesity and the like, the secretion volume of beneficial adipocytokines decreased, whereas harmful adipocytokines are secreted in excess. As a result, the balance between these adipocytokines is disturbed, presumably leading to the development of lifestyle-related diseases such as type II diabetes mellitus and arteriosclerosis.
As described above, adiponectin is associated with obesity and lifestyle-related diseases caused by obesity, and it is assumed that activation of this adiponectin is effective for the prevention or treatment of lifestyle-related diseases. Further, adiponectin is also known to have an inhibitory effect on hepatic fibrosis. Adiponectin has been shown to have a wide variety of actions such as improvement of hypertension, fat metabolism, and insulin sensitivity, an anti-inflammatory action, suppression of hepatic fibrosis, a facilitatory effect on the proliferation of normal hepatocytes (Patent Document 1), and an anti-inflammatory effect (Patent Document 2) (Patent Documents 2 to 5), suggesting that a drug, drink, or food which increases the blood concentration of adiponectin has a preventive or amelioratingactivity on metabolic syndrome.
Under such a background, a thiazolidine derivative is known as a drug promoting the production of adiponectin. However, this thiazolidine derivative may cause side effects such as digestive symptoms such as diarrhea, constipation, and queasy feeling as well as hepatic dysfunction.
Furthermore, some compounds or components which promote the production of adiponectin are proposed. For example, Patent Document 6 discloses that N-acetylcysteine increases the expression level of adiponectin in adipocytes, and apocynin increases the plasma concentration of adiponectin and also the expression level of adiponectin in adipose tissue. Patent Document 7 discloses that a gingerol compound enhances the production of adiponectin, and Patent Document 8 discloses that amla fruit or its extract enhances the production of adiponectin. Besides these, excellent adiponectin production promoting substances are still demanded. Accordingly, under present circumstances in which countermeasures against metabolic syndrome have become a social issue, development of a safe substance which has an action of promoting and enhancing in vivo production of adiponectin has been demanded.